Oestrogen May Raise Brain Drug Levels in Women
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- Davunetide, derived from the brain protein ADNP by Illana Gozes at Tel Aviv University more than 20 years ago, failed a pivotal 2014 late-stage trial for progressive supranuclear palsy, leading Allon Therapeutics to halt its development.
- Reanalysis of trial data by Gozes and colleagues found that in women with progressive supranuclear palsy, davunetide appeared to slow disease progression and protect against symptoms such as difficulty swallowing and speaking.
- In experiments with female mice given fluorescently labeled davunetide, more of the drug reached the head when oestrogen levels were highest; in a small group of 8 human volunteers (6 women, 2 men), women tended to have higher peak plasma concentrations.
- Oestrogen can influence blood flow, drug metabolism, and the permeability of the blood-brain barrier, which Gozes says may explain the sex-based differences in drug absorption observed in the study.
- Jens Pahnke at the University of Oslo, who was not involved in the research, cautioned the findings are based on mice and a small human cohort, but agreed with Gozes that hormonal status is rarely measured in clinical trials — even when results are split by sex — potentially obscuring key sources of biological variation.
- Davunetide is now licensed to ExoNavis Therapeutics in Tel Aviv, where Gozes serves as VP of drug development; the company is planning sex-stratified clinical trials in ADNP syndrome, progressive supranuclear palsy, and other conditions.
Why it matters: Gozes and Pahnke argue that clinical trials for brain-targeted drugs rarely track hormonal status even when data is sex-stratified, meaning a potentially effective compound for women may have been shelved for over a decade. With davunetide now back in development at ExoNavis Therapeutics with planned sex-stratified trials, the case is being positioned as a template for re-evaluating other failed neurological drugs that may have worked in one sex but not the other.
